Biomedical subjects
R C Leonard
Publications and source records attributed to R C Leonard.
Optimising antiemesis in cancer chemotherapy: efficacy of continuous versus intermittent infusion of high dose metoclopramide in emesis induced by cisplatin.
Thirty three untreated patients being given cisplatin received metoclopramide (7 mg/kg) for antiemesis by either continuous or intermittent infusion in a random order. Each patient received intravenous dexamethasone in addition. High pressure liquid chromatography was used to measure plasma concentrations of metoclopramide. The two regimens were evaluated for antiemetic efficacy and the incidence of side effects. The intermittent metoclopramide regimen resulted in peak and trough plasma concentrations of metoclopramide with accumulation at eight hours, while the loading dose and continuous infusion resulted in mean plasma concentrations greater than 0.85 micrograms/ml (2.8 mumol/l) throughout the eight hour period. The continuous infusion was associated with a significant improvement in nausea and vomiting and reduction in diarrhoea. Major control of emesis (two episodes or fewer) was achieved in 27 patients receiving continuous metoclopramide compared with 18 receiving intermittent metoclopramide.
Dexamethasone antiemesis and side-effects.
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Anti-emetic efficacy of dexamethasone in combination for out-patients receiving cytotoxic chemotherapy.
A single blind randomised trial of two different anti-emetic regimens (A and B) was performed in 26 patients with breast carcinoma undergoing emetic i.v. cytotoxic chemotherapy. They all received oral Motival (nortriptylene/fluphenazine) for 48 h after therapy and for regimen A received N-saline i.v. with their cytotoxics whilst for regimen B patients were given 16 mg dexamethasone i.v. Patients were given the alternative regimen at the subsequent course of treatment. They were asked to assess overall nausea and number of vomiting episodes in the 24 h following therapy. There was a statistically significant reduction in both for the regimen containing dexamethasone. This agent causes few side effects and is particularly suited for out-patient use.
The clinical pharmacology of mitozantrone.
The pharmacological disposition of the anthracenedione mitozantrone has been measured in 11 patients with six different tumour types. Administered at 14 mg/m2 as a 30-min infusion, the drug was assayed by a high-pressure liquid chromatographic technique sensitive to 1 ng mitozantrone/ml plasma. The mean half-lives for mitozantrone in plasma were as follows: alpha, 9.4 min; beta, 1.6 h; gamma, 23 h. The mean volume of distribution (Vd) was 1565 l. For two patients with impaired liver function the T1/2 gamma and Vd were 63.1 h and 4853 l, respectively. Less than 5% of the administered drug was excreted in urine, but two urinary metabolites were identified. These were not influenced by pre incubation of urine samples with beta-glucuronidase or sulphatase, suggesting that neither metabolite is a glucuronide or a sulphate conjugate of mitozantrone. Hepatic metabolism is the major route of elimination of mitozantrone, and caution should be exercised when using this drug for patients with hepatic dysfunction.
The impact of chemotherapy on small cell carcinoma of the bronchus.
Between 1971 and 1978, 140 cases of small cell anaplastic carcinoma of the bronchus were registered by a group of chest physicians in north Edinburgh. Sixty-five of these patients received specific treatment either with radiotherapy or cyclophosphamide and 75 patients were given treatment for symptoms only. Between 1979 and 1981 83 patients referred to the same physicians and pathologists were treated with combination chemotherapy (methotrexate, cyclophosphamide and CCNU) for 12 weeks. Overall median survival in the 1971 to 1978 group was two months with the actively-treated patients surviving for five months vs. less than one month for treatment of symptoms only. For the 83 patients treated with combination chemotherapy, median survival was nine months with 33 per cent alive at one year and 13 per cent at two years. Positive factors associated with prolonged survival included performance status at presentation and response to chemotherapy. This study demonstrates that the prognosis for the majority of patients with small cell carcinoma of the bronchus has improved significantly with the introduction of combination chemotherapy.
Protective effect of sodium-2-mercaptoethanesulfonate on the gastrointestinal toxicity and lethality of cis-diamminedichloroplatinum.
cis-Diamminedichloroplatinum (cis-platinum) is an effective and widely used antitumor drug. Patients receiving cis-platinum, however, experience very profound and long lasting gastrointestinal symptoms. The role of intestinal mucosal toxicity in the pathogenesis of these symptoms is unclear. In this study we have investigated the thiol-containing compound mesna (sodium-2-mercaptoethanesulfonate) as a potential antidote to cis-platinum-induced gastrointestinal tract damage. In mice, mesna caused a significant reduction in the gastrointestinal toxicity of cis-platinum assessed by electron microscopy, villus recovery rate, and by disaccharidase estimations. Mesna also significantly reduced serum creatinine levels following cis-platinum. Administration of mesna prior (or immediately following) a 67% lethal dose of cis-platinum protected 87-100% of the animals from the lethal effects. The antitumor efficacy of cis-platinum in L1210 leukemia bearing mice was not affected by coadministration of mesna indicating that the protective effect may be tissue specific. In addition this finding indicates that mesna has potential as an agent which may improve the therapeutic index of cis-platinum in clinical practice.
Metoclopramide versus chlorpromazine in controlling nausea and vomiting induced by cytotoxic drugs.
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Tamoxifen as primary treatment of breast cancer in elderly or frail patients: a practical management.
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cis-Platinum and vindesine in combination in the treatment of non-small cell lung cancer.
Sixty-three patients with advanced non-small cell carcinoma of the bronchus were treated with a combination of cis-platinum and vindesine. All patients had measurable disease and were of good performance status; none had received prior chemotherapy or radiotherapy. Thirty-three per cent of patients responded, with five patients achieving complete remission. Median duration of response was 4 months, with a median survival of 14 months in the responsers, compared with 6.5 months in the whole group and 4.8 months in the nonresponders. Severe toxicity was encountered, with alopecia, gastrointestinal toxicity and neurotoxicity common. Myelosuppression and renal toxicity were not dose-limiting. Thus the activity of this drug combination is confirmed, but severe toxicity precludes its widespread use in clinical practice.
The heterogeneity of human cancers and its influence on metastases and therapy.
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Acute pancreatitis in association with small cell lung carcinoma: potential pitfall in diagnosis and management.
Tumour metastases to the pancreas are a rare but recognized cause of acute pancreatitis, there is a 24-40% incidence of pancreatic involvement from small cell lung cancer in autopsy series but only a very few cases of tumour-induced acute pancreatitis have been described. Chemotherapy has been advocated as the primary therapy in patients with known oat cell carcinoma who develop acute pancreatitis. We describe 2 patients with acute haemorrhagic pancreatitis in association with disseminated small cell carcinoma but without evidence of tumour invasion in the gland and with gall stones present in the gall bladder. Chemotherapy would have been inappropriate therapy for these patients.
Gallium scanning by conventional imaging and emission computed tomography in the pretreatment evaluation of lung cancer.
Gallium 67 citrate was evaluated with conventional scanning and emission computed tomography (CT) scanning as a method of pretreatment staging of the intrathoracic, especially mediastinal, spread of lung cancer. Of 31 patients with tumours of various histological types, the isotope was concentrated in the primary lesion in all but one. In 10 out of 12 patients who underwent surgical exploration conventional gallium scanning correctly indicated the mediastinum to be clear and identified two other patients with a tumour of the mediastinum not recognised by chest radiography or emission CT gallium scanning. Neither conventional nor emission CT gallium scanning produced false positive images. Conventional gallium scanning can give information about the mediastinum not available from chest radiographs or bronchoscopy.
Role of 99mTc methylene diphosphonate bone imaging in the management of lymphoma.
The role of modern techniques of 99mTc methylene diphosphonate bone imaging in the management of lymphoma patients was assessed by comparing results of 107 bone scans in 16 patients with Hodgkin's disease, and 45 patients with non-Hodgkin's lymphoma to simultaneous radiologic, clinical, and histopathologic features as well as to subsequent disease course. The sensitivity and specificity were both greater than or equal to 0.96 in both Hodgkin's disease and non-Hodgkin's lymphoma and the overall accuracy by site was 98%. The scan proved to be useful in the definition and follow-up of skeletal lymphomatous disease in both symptomatic and asymptomatic patients, and defined abnormalities which were not predicted by either serum alkaline phosphatase activity or the presence of bone marrow involvement. In no patient, however, did the bone scan result by itself alter either initial staging or estimates of extent of disease at the time of relapse. Bone scanning, therefore, cannot be recommended as a screening procedure in patients with lymphoma; rather, this test is best reserved for the definition and follow-up of skeletal metastases in patients with active, concomitant, extraosseous disease.
Dexamethasone and high dose metoclopramide: efficacy in controlling cisplatin induced nausea and vomiting.
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Paraneoplastic hypercalcaemia in ovarian carcinoma.
Five patients were seen in whom a raised serum calcium concentration was associated with ovarian carcinoma (clear cell in two cases, cystadenocarcinoma in three). None showed evidence of metastases in bone. The hypercalcaemia occurred as a paraneoplastic phenomenon, but biochemical studies suggested the production of a parathyroid-hormone-like substance. One patient remained free of symptoms of her hypercalcaemia throughout. Paraneoplastic hypercalcaemia due to ovarian carcinoma may be more common than generally recognised and present as a life threatening condition requiring urgent treatment.
Dystonic reactions due to metoclopramide.
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Phase II trial of vindesine and VP16-213 in the palliation of poor-prognosis patients and elderly patients with small cell lung cancer.
Forty-three previously untreated patients, all of whom had poor-prognosis small cell lung cancer and/or were greater than 65 years old, received treatment with vindesine and VP16-213. Thirteen patients had limited disease and 30 extensive disease. Response rates (CR + PR) of 86% (CR 29%) and 66% (CR 17%) were seen in patients with limited and extensive disease, respectively. Time to relapse was short in those responding (4-4.5 months), and most responders required additional treatments. The overall toxicity was minimal and patient compliance was high. This combination is useful for the palliative treatment of small cell lung cancer when aggressive chemotherapy is inappropriate.